Severity Of Post-cardiac Arrest Syndrome Research Articles

Differential Effectiveness of Hypothermic Targeted Temperature Management According to the Severity of Post-Cardiac Arrest Syndrome.

International guidelines recommend targeted temperature management (TTM) to improve the neurological outcomes in adult patients with post-cardiac arrest syndrome (PCAS). However, it still remains unclear if the lower temperature setting (hypothermic TTM) or higher temperature setting (normothermic TTM) is superior for TTM. According to the most recent large randomized controlled trial (RCT), hypothermic TTM was not found to be associated with superior neurological outcomes than normothermic TTM in PCAS patients. Even though this represents high-quality evidence obtained from a well-designed large RCT, we believe that we still need to continue investigating the potential benefits of hypothermic TTM. In fact, several studies have indicated that the beneficial effect of hypothermic TTM differs according to the severity of PCAS, suggesting that there may be a subgroup of PCAS patients that is especially likely to benefit from hypothermic TTM. Herein, we summarize the results of major RCTs conducted to evaluate the beneficial effects of hypothermic TTM, review the recent literature suggesting the possibility that the therapeutic effect of hypothermic TTM differs according to the severity of PCAS, and discuss the potential of individualized TTM.

Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study.

To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure. Randomized blinded study (animal model). University animal research facility. Twenty-four adult male "New Zealand White" rabbits. Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period. Pupillary reactivity (primary outcome), levels of S100β protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100β protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis. Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.

Outcome Related to Level of Targeted Temperature Management in Postcardiac Arrest Syndrome of Low, Moderate, and High Severities: A Nationwide Multicenter Prospective Registry.

The optimal target temperature during targeted temperature management for patients after cardiac arrest remains under debate. The aim of this study was to evaluate the association between targeted temperature management at lower target temperatures and the neurologic outcomes among patients classified by the severity of postcardiac arrest syndrome. A multicenter observational study from the out-of-hospital cardiac arrest registry of the Japanese Association for Acute Medicine, which is a nationwide prospective registry of out-of-hospital cardiac arrest patients. A total of 125 critical care medical centers or hospitals with an emergency care department across Japan. A total of 1,111 out-of-hospital cardiac arrest patients who had received targeted temperature management. We divided all 1,111 postcardiac arrest syndrome patients treated with targeted temperature management into two groups: those who received targeted temperature management at a lower target temperature (33-34°C) and those who received targeted temperature management at a higher target temperature (35-36°C). In regard to classification of the patients, we divided the patients into three categories of severity (low, moderate, and high severities) using the risk classification tool, post-Cardiac Arrest Syndrome for Therapeutic hypothermia, which was previously validated. The primary outcome was the percentage of patients with a good neurologic outcome at 30 days, and the secondary outcome was the survival rate at 30 days. Multivariate analysis showed that targeted temperature management at 33-34°C was significantly associated with a good neurologic outcome and survival at 30 days in the moderate severity (odds ratio, 1.70 [95% CI, 1.03-2.83] and 1.90 [95% CI, 1.15-3.16], respectively), but not in the patients of low or high severity (pinteraction = 0.033). Propensity score analysis also showed that targeted temperature management at 33-34°C was associated with a good neurologic outcome in the moderate-severity group (p = 0.022). Targeted temperature management at 33-34°C was associated with a significantly higher rate of a good neurologic outcome in the moderate-severity postcardiac arrest syndrome group, but not in the low- or high-severity group.

Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

BackgroundResuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose at admission are at high risk of morbidity and mortality. This has been attributed to the post-cardiac arrest syndrome (PCAS) which encompasses multiple interacting components, including systemic inflammation. Elevated levels of circulating interleukin-6 (IL-6), a pro-inflammatory cytokine, is associated with worse outcomes in OHCA patients, including higher vasopressor requirements and higher mortality rates. In this study, we aim to reduce systemic inflammation after OHCA by administering a single infusion of tocilizumab, an IL-6 receptor antibody approved for use for other indications.MethodsInvestigator-initiated, double-blinded, placebo-controlled, single-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Brief inclusion criteria: OHCA of presumed cardiac cause, persistent unconsciousness, age ≥ 18 years. Intervention: 80 patients will be randomized in a 1:1 ratio to a single 1-h intravenous infusion of either tocilizumab or placebo (NaCl). During the study period, patients will receive standard of care, including sedation and targeted temperature management of 36 ° for at least 24 h, vasopressors and/or inotropes as/if needed, prophylactic antibiotics, and any additional treatment at the discretion of the treating physician. Blood samples are drawn for measurements of biomarkers included in the primary and secondary endpoints during the initial 72 h. Primary endpoint: reduction in C-reactive protein (CRP). Secondary endpoints (abbreviated): cytokine levels, markers of brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, adverse events, and follow-up assessment of cerebral function and mortality.DiscussionWe hypothesize that reducing the effect of circulating IL-6 by administering an IL-6 receptor antibody will mitigate the systemic inflammatory response and thereby modify the severity of PCAS, in turn leading to lessened vasopressor use, more normal hemodynamics, and better organ function. This will be assessed by primarily focusing on hemodynamics and biomarkers of organ damage during the initial 72 h.In addition, pro-inflammatory and anti-inflammatory cytokines will be measured to assess if cytokine patterns are modulated by IL-6 receptor blockage.Trial registrationClinicalTrials.gov Identifier: NCT03863015; submitted February 22, 2019, first posted March 5, 2019.EudraCT: 2018-002686-19; date study was authorized to proceed: November 7, 2018.

Cardiac function after cardiac arrest: what do we know?

Postcardiac arrest myocardial dysfunction (PCAMD) is a frequent complication faced during post-resuscitation care that adversely impacts survival and neurological outcome. Both mechanical and electrical factors contribute to the occurrence of PCAMD. Prearrest ventricular function, the cause of cardiac arrest, global ischemia, resuscitation factors, ischemia/reperfusion injury and post-resuscitation treatments contribute to the severity of PCMAD. The pathophysiology of PCAMD is complex and include myocytes energy failure, impaired contractility, cardiac edema, mitochondrial damage, activation of inflammatory pathways and the coagulation cascade, persistent ischemic injury and myocardial stiffness. Hypotension and low cardiac output with vasopressor/inotropes need are frequent after resuscitation. However, clinical, hemodynamic and laboratory signs of shock are frequently altered by cardiac arrest pathophysiology and post-resuscitation treatment, potentially being misleading and not fully reflecting the severity of postcardiac arrest syndrome. Even if validated criteria are lacking, an extensive hemodynamic evaluation is useful to define a "benign" and a "malign" form of myocardial dysfunction and circulatory shock, potentially having treatment and prognostic implications. Cardiac output is frequently decreased after cardiac arrest, particularly in patients treated with target temperature management (TTM); however, it is not independently associated with outcome. Sinus bradycardia during TTM seems independently associated with survival and good neurological outcome, representing a promising prognostic indicator. Higher mean arterial pressure (MAP) seems to be associated with improved survival and cerebral function after cardiac arrest; however, two recent randomized clinical trials failed to replicate these results. Recommendations on hemodynamic optimization are relatively poor and are largely based on general principle of intensive care medicine.

The predictive value of serum procalcitonin level as a prognostic marker for outcomes in out-of-hospital cardiac arrest patients

Background: Patients who have successful return of spontaneous circulation after cardiac arrest may experience post-cardiac arrest syndrome. Procalcitonin can be used to assess the severity of post-cardiac arrest syndrome. The association between procalcitonin and outcomes in Asian patients with post-cardiac arrest syndrome has not been extensively studied. Objective: This study aimed to investigate the predictive value of serum procalcitonin level in the prognosis of patients hospitalized after out-of-hospital cardiac arrest. Methods: A retrospective observational study using the multicenter Korean Cardiac Arrest Research Consortium registry between October 2015 and June 2018 was performed. Serum procalcitonin level at the early phase of hospital presentation was obtained from the patients hospitalized after out-of-hospital cardiac arrest. In-hospital mortality and neurologic outcomes at hospital discharge were estimated. The relationship between serum procalcitonin level and in-hospital mortality and neurologic outcomes of patients was analyzed. Results: A total of 254 patients hospitalized after out-of-hospital cardiac arrest were included. Serum procalcitonin level was significantly elevated in non-survivors compared to survivors (0.17 (0.05–0.18) ng/dL vs. 0.10 (0.05–0.39) ng/dL, p = 0.017, respectively). In addition, serum procalcitonin level was significantly elevated in patients with unfavorable outcomes at hospital discharge compared to those with favorable outcomes (0.16 (0.06–1.10) ng/dL vs. 0.07 (0.04–0.22) ng/dL, p &lt; 0.001, respectively). However, serum procalcitonin level had a weak predictive value for in-hospital mortality (area under the receiver operating characteristic curve: 0.587, 95% confidence interval: 0.517–0.657, p = 0.017, cut-off = 0.12 ng/dL, specificity = 57.4%) and unfavorable outcomes (area under the receiver operating characteristic curve: 0.646, 95% confidence interval: 0.571–0.721, p &lt; 0.001, cut-off = 0.11 ng/dL, specificity = 62.3%). Conclusion: Elevated serum procalcitonin level in patients hospitalized after out-of-hospital cardiac arrest at the early phase of hospital presentation is associated with poor outcomes. However, serum procalcitonin level had weak diagnostic accuracy for predicting in-hospital mortality and unfavorable outcomes.

Limb Ischemic Postconditioning Alleviates Postcardiac Arrest Syndrome through the Inhibition of Mitochondrial Permeability Transition Pore Opening in a Porcine Model.

Objective Previously, the opening of mitochondrial permeability transition pore (mPTP) was confirmed to play a key role in the pathophysiology of postcardiac arrest syndrome (PCAS). Recently, we demonstrated that limb ischemic postconditioning (LIpostC) alleviated cardiac and cerebral injuries after cardiac arrest and resuscitation. In this study, we investigated whether LIpostC would alleviate the severity of PCAS through inhibiting mPTP opening. Methods Twenty-four male domestic pigs weighing 37 ± 2 kg were randomly divided into three groups: control, LIpostC, and LIpostC+atractyloside (Atr, the mPTP opener). Atr (10 mg/kg) was intravenously injected 30 mins prior to the induction of cardiac arrest. The animals were subjected to 10 mins of untreated ventricular fibrillation and 5 mins of cardiopulmonary resuscitation. Coincident with the beginning of cardiopulmonary resuscitation, LIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results After resuscitation, systemic inflammation and multiple organ injuries were observed in all resuscitated animals. However, postresuscitation systemic inflammation was significantly milder in the LIpostC group than in the control group. Myocardial, lung, and brain injuries after resuscitation were significantly improved in the LIpostC group compared to the control group. Nevertheless, pretreatment with Atr abolished all the protective effects induced by LIpostC. Conclusion LIpostC significantly alleviated the severity of PCAS, in which the protective mechanism was associated with the inhibition of mPTP opening.

Abstract 106: Differential Effects of Mild Therapeutic Hypothermia Against Normothermia for Post-Cardiac Arrest Syndrome According to the Severity Scale

Introduction: There are few studies on the differential effects of mild therapeutic hypothermia (MTH) according to the risk class in post-cardiac arrest syndrome (PCAS) patients. Objective: The aim of this study was to evaluate the differential effects of MTH against therapeutic normothermia (TN) for PCAS patients according to our risk classification tool (rCAST). Methods: We used data from the out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM), which is a multi-center, prospective registry of OHCA patients who were transported to critical care medical centers or hospitals with an emergency care department across Japan. We classified eligible PCAS patients treated with MTH or TN on the basis of our rCAST score which was previously developed by us: low severity group (≤5.5), moderate severity group (6-14), and high severity group (≥14.5). The differential effects of MTH vs. TN for their neurological outcome in the 3 severity categories were evaluated by interaction analysis, and the effect of MTH vs. TN in each group was assessed by multivariate logistic regression analysis and propensity score analysis. The good neurological outcome was defined as a Cerebral Performance Categories score ≤2 at 30 days. Results: Among 12,024 OHCA patients in the registry, data of 460 PCAS patients treated by MTH or TN were analyzed (96 patients; the low score, 192; the moderate score, and 172; the high score group). There was a statistically significant interaction effect between MTH/TN and their neurological outcome at 30 days in the 3 categories (p = 0.022). MTH was significantly associated with good neurological outcome at 30 days in PCAS patients of moderate severity group both in the multivariate logistic regression analysis (adjusted odds ratio, 3.09; 95% confidence interval, 1.13-8.49; p = 0.029) and the propensity score analysis (p = 0.030), while it was not in low and high severity group. Conclusions: The effect of MTH in PCAS patients differed according to the severity of PCAS, and MTH was significantly associated with a good neurological outcome as compared to TN in the moderate severity group.

Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest.

Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest. As a subcohort analysis of a prospective, observational, multicenter study "FINNRESUSCI," we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models. Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68-0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65-0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome. Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.

Duration of Untreated Cardiac Arrest and Clinical Relevance of Animal Experiments: The Relationship Between the "No-Flow" Duration and the Severity of Post-Cardiac Arrest Syndrome in a Porcine Model.

The study investigated the effect of untreated cardiac arrest (CA), that is, "no-flow" time, on postresuscitation myocardial and neurological injury, and survival in a pig model to identify an optimal duration that adequately reflects the most frequent clinical scenario. An established model of myocardial infarction followed by CA and cardiopulmonary resuscitation was used. Twenty-two pigs were subjected to three no-flow durations: short (8-10 min), intermediate (12-13 min), and long (14-15 min). Left ventricular ejection fraction (LVEF) was assessed together with thermodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT). Neurological impairment was evaluated by neurological scores, serum neuron specific enolase (NSE), and histopathology. More than 60% of animals survived when the duration of CA was ≤13 min, compared to only 20% for a duration ≥14 min. Neuronal degeneration and neurological scores showed a trend toward a worse recovery for longer no-flow durations. No animals achieved a good neurological recovery for a no-flow ≥14 min, in comparison to a 56% for a duration ≤13 min (P = 0.043). Serum NSE levels significantly correlated with the no-flow duration (r = 0.892). Longer durations of CA were characterized by lower LVEF and CO compared to shorter durations (P < 0.05). The longer was the no-flow time, the higher was the number of defibrillations delivered (P = 0.043). The defibrillations delivered significantly correlated with LVEF and plasma hs-cTnT. Longer no-flow durations caused greater postresuscitation myocardial and neurological dysfunction and reduced survival. An untreated CA of 12-13 min may be an optimal choice for a clinically relevant model.

Endothelial activation/injury and associations with severity of post-cardiac arrest syndrome and mortality after out-of-hospital cardiac arrest

BackgroundPost-cardiac arrest syndrome (PCAS) is characterized by whole-body ischemia triggering systemic inflammation and damage of the endothelium. This study investigated the relationship between systemic inflammation, endothelial damage and severity of PCAS and the association between endothelial damage and outcome after out-of-hospital cardiac arrest (OHCA). MethodsIn this post hoc study, we analyzed 163 comatose patients included at a single center in the target temperature management (TTM) trial, randomly assigned to TTM at 33°C or 36°C for 24h. Endothelial biomarkers (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin) and the inflammatory biomarker interleukin-6 (IL-6) were measured at admission (baseline) and 24, 48 and 72h after OHCA. Severity of PCAS was assessed by Sequential Organ Failure Assessment score. Mortality at 30-days was evaluated by Cox regression analysis. ResultsBy linear regression, baseline IL-6 levels (two-fold) was independently associated with glycocalyx damage (syndecan-1 (10.3ng/ml (p=0.01))), endothelial activation (sE-selectin (2.0ng/ml (p=0.03))) and endothelial damage (thrombomodulin 0.7ng/ml (p=0.0005)) at 24h after OHCA. Adjusted for baseline IL-6, a two-fold increase in thrombomodulin from baseline to 48h (1.7 (0.9–2.4), p<0.0001) and 72h (1.5 (0.6–2.3), p<0.0007) was more closely associated with severity of PCAS than IL-6. Levels of syndecan-1, thrombomodulin and sVE-cadherin was not influenced by level of target temperature but levels of sE-selectin was significantly lower in the 36°C group (−55ng/ml (95%CI: −53 to −58ng/ml), p=0.005) compared to the 33°C group. High levels of thrombomodulin at 24h (HR=2.1 (1.3–3.3), p=0.001) and 48h (HR=1.75 (1.0–2.8), p=0.02) were associated with increased 30-day mortality in univariate analysis, but not in multivariable analyses. ConclusionIn comatose survivors after OHCA treated with TTM, systemic inflammation was associated with endothelial activation and endothelial damage. Sustained endothelial damage was independently associated with severity of PCAS, adjusted for level of systemic inflammation. TTM at 36°C compared to 33°C after OHCA was associated with lower endothelial activation, but not endothelial damage.Clinical Trial Registration: URL: clinicaltrials.gov/ct2/show/NCT01020916. Unique identifier: NCT01020916

Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest.

BackgroundAn intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome.MethodsPlasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score ≥ 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed.ResultsEighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6–31.3] ng/mL, and persisted high 48 h later, 14.8 [9.8–31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p < 0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7–60.1] ng/mL vs. 13.6 [9.1–26.2] ng/mL, p < 0.0001; AUC = 0.70 ± 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7–78.2] ng/mL) compared to those who survived (13.5 [9.1–25.5] ng/mL, p < 0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3–44.3] ng/mL vs. 12.8 [8.6–30.4] ng/mL, p < 0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74 ± 0.04 (p < 0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076–2.399], p = 0.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834–1.596], p = 0.387).ConclusionsElevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1412-4) contains supplementary material, which is available to authorized users.

Abstract 18190: Associations Between Endothelial Injury, Severity of Post-cardiac Arrest Syndrome and Mortality After Out-of-hospital Cardiac Arrest

Background: Post-cardiac arrest syndrome (PCAS) is characterized by systemic inflammation and endothelial dysfunction, which may exacerbate organ failure and may be related to adverse outcome. We sought to investigate the associations between trombomodulin (TM), a marker of endothelial cell injury, and severity of PCAS and the possible prognostic importance in comatose survivors of out-of-hospital cardiac arrest treated with targeted temperature management (TTM). Methods: We included 163 patients, randomly assigned to TTM at 33°C or 36°C for 24 h in the TTM-trial at a single center. Serum TM was analyzed at 0, 24, 48 and 72 hours after cardiac arrest and stratified in median value of TM for outcome analysis at each time point to a high or low TM group. Severity of PCAS was assessed daily by the Sequential Organ Failure Assessment score. Survival status was recorded at 180 days. Results: Corresponding values of TM and severity of PCAS correlated at each time point, baseline (r=0.31, p=0.0001), 24 h (r=0.52, p&lt;0.0001), 48 h (r=0.50, p&lt;0.0001) and 72 h (r=0.36, p&lt;0.0001). Levels of TM changed significantly within the first 3 days (p&lt;0.0001) with no significant difference between temperature groups, p interaction =0.32. At 24 h, the 180-day mortality rate in patients with high TM levels (&gt; 6.9 ng·ml -1 = median) was 42% compared to 18% in patients with low TM levels, p=0.002 (Figure), corresponding to an unadjusted hazard ratio of 2.6 (95%CI: 1.4-4.9), p=0.003. When adjusting for pre-hospital prognostic factors the hazard ratio for high TM levels at 24 h was 1.5 (95%CI: 0.7-3.1), p=0.31, with no significant interaction between level of TM and TTM-group, p=0.74. Analysis of TM at 48 and 72 hours showed similar results. Conclusions: Levels of TM are significantly elevated and associated with severity of PCAS with no effect of target temperature at 33°C or 36°C. High TM levels were associated with increased mortality, but the association was explained by confounding factors.

The inflammatory response after out-of-hospital cardiac arrest is not modified by targeted temperature management at 33 °C or 36 °C

AimSurvivors after cardiac arrest (CA) exhibits a systemic inflammatory response as part of post-cardiac arrest syndrome (PCAS). We investigated the association between systemic inflammation and severity of PCAS and whether level of targeted temperature management (TTM) modifies level of the inflammatory response. MethodsWe studied 169 patients included at a single center in the TTM-trial, randomly assigned to TTM at 33°C or 36°C for 24h. Plasma samples were analyzed for inflammatory markers including interleukin (IL) IL-1β,IL-4,IL-6,IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and procalcitonin (PCT) at randomization and 24, 48 and 72h after CA. Severity of PCAS was assessed by Sequential Organ Failure Assessment (SOFA) score. ResultsPlasma levels of both IL-6 and IL-10 determined at randomization correlated with severity of PCAS at day 2 (r=0.36 and r=0.27, p<0.001) and day 3 (r=0.32 and r=0.22, p<0.001). IL-6 at randomization was an independent predictor of severity of PCAS at day 2 (p=0.003) and day 3 (p<0.0001) and was a significantly stronger predictor of severity of PCAS at day 3 compared to CRP (p=0.04) and PCT (p=0.03). Level of TTM did not modify level of the inflammatory markers IL-1β, IL-6, TNF-α, IL-4, IL-10, CRP and PCT, (p=NS for each inflammatory marker). ConclusionsLevel of inflammatory response was associated with severity of PCAS with IL-6 being consistently and more strongly associated with severity of PCAS than the inflammatory markers CRP and PCT. The systemic inflammatory response after CA was not modified by TTM at 33°C or 36°C.

Serum procalcitonin as a marker of post-cardiac arrest syndrome and long-term neurological recovery, but not of early-onset infections, in comatose post-anoxic patients treated with therapeutic hypothermia

ObjectiveTo examine the relationship of early serum procalcitonin (PCT) levels with the severity of post-cardiac arrest syndrome (PCAS), long-term neurological recovery and the risk of early-onset infections in patients with coma after cardiac arrest (CA) treated with therapeutic hypothermia (TH). MethodsA prospective cohort of adult comatose CA patients treated with TH (33°C, for 24h) admitted to the medical/surgical intensive care unit, Lausanne University Hospital, was studied. Serum PCT was measured early after CA, at two time-points (days 1 and 2). The SOFA score was used to quantify the severity of PCAS. Diagnosis of early-onset infections (within the first 7 days of ICU stay) was made after review of clinical, radiological and microbiological data. Neurological recovery at 3 months was assessed with Cerebral Performance Categories (CPC), and was dichotomized as favorable (CPC 1–2) vs. unfavorable (CPC 3–5). ResultsFrom December 2009 to April 2012, 100 patients (median age 64 [interquartile range 55–73] years, median time from collapse to ROSC 20 [11–30]min) were studied. Peak PCT correlated with SOFA score at day 1 (Spearman's R=0.44, p<0.0001) and was associated with neurological recovery at 3 months (peak PCT 1.08 [0.35–4.45]ng/ml in patients with CPC 1–2 vs. 3.07 [0.89–9.99] ng/ml in those with CPC 3–5, p=0.01). Peak PCT did not differ significantly between patients with early-onset vs. no infections (2.14 [0.49–6.74] vs. 1.53 [0.46–5.38]ng/ml, p=0.49). ConclusionsEarly elevations of serum PCT levels correlate with the severity of PCAS and are associated with worse neurological recovery after CA and TH. In contrast, elevated serum PCT did not correlate with early-onset infections in this setting.